This invention relates to the formation of liquid core capsules utilizing interfacial polymerization. More particularly, this invention relates to the encapsulation of liquid particles within nanometer thick polymer shells utilizing an interfacial free radical alternating copolymerization process.
Liquid-core capsules have wide-ranging applications in the high efficiency encapsulation and controlled delivery of drugs, dyes, enzymes, and many other biological substrates. These important applications have driven the rapid development of innovative techniques, based on layer-by-layer assembly, shell polymerization of particles and dendrimers followed by core-removal, microphase separation of core-shell latexes, and vesicles, to confine polymerization or assembly of encapsulants at the interface.
Interfacial polymerizations based on the reactions of amines and acid chlorides, lactide diols and diketene acetals, isocyanates and alcohols, isocyanates and amines, or urea and formaldehyde have been used to form liquid-core polymer capsules. As it stands however, monomers for these polymerizations react immediately upon contact and/or hydrolyze when finely dispersed in water. Thus, capsules smaller than 1 micron are difficult to prepare reliably. Moreover, the chemistry of these step polymerizations intrinsically requires two different chemical functionalities. Choices for a third functionality, e.g., acidic/basic or charged groups to allow for pH/ionic strength control of shell permeability without interfering with the polymerization, are thus very limited.
In traditional free-radical interfacial polymerizations, a macromer solution, which is a polymerizable pre-polymer, that optionally contains a co-catalyst, is applied to a material. The macromer is then polymerized with a free radical initiator that is adsorbed onto the surface of the material to be coated while the non-adsorbed initiator is rinsed off by a rinsing solution or by application of a macromer solution. One example of interfacial polymerization is the Microcapsule Interfacial Polymerization Method. Biological materials can be encapsulated as described above with reference to suspension polymerization, but utilizing interfacial polymerization to form the membrane on the surface of the biological material or microcapsule. This involves coating the biological material or microcapsule with a photoinitiator, suspending the biological material or microcapsules in the macromer solution, and immediately polymerizing the mixture, for example, by irradiating. A thin polymer coat, of less than 50 microns thickness can be formed around the biological materials or the microcapsule since the photoinitiator is present only at the microcapsule surface and is given insufficient time to diffuse far into the macromer solution.
In most cases, the initiator, such as a dye, will penetrate into the interior of the biological material or the microcapsule, as well as adsorbing to the surface. When macromer solution, optionally containing a cocatalyst such as triethanolamine, is applied to the surface and exposed to an initiating agent such as laser light, all the essential components of the reaction are present only at and just inside the interface of the biological material or microcapsule and macromer solution. Hence, polymerization and gelation (if multifunctional macromer is used), which typically occurs within about 100 msec, initially takes place only at the interface, just beneath it, and just beyond it. If left for longer periods of time, initiator starts diffusing from the inner core of the microsphere into the solution; similarly, macromers start diffusing inside the core and a thicker layer of polymer is formed.
Another example of an interfacial polymerization technique is the Direct Interfacial Polymerization Method, which promotes the formation of a membrane directly onto the surface of materials of interest that include, for example, cells and tissue. In this process, the material is directly coated with initiator, excess initiator is removed, the macromer solution is applied to the tissue and then polymerized.
Although encapsulation of materials through the use of interfacial polymerization exists, there is a need for a direct approach to preparing liquid-core capsules capable of controlling the shell thickness using interfacial free radical alternating copolymerization.